The relationship between mast cell-mediator release and nonspecific bronchial reactivity was investigated in allergen-induced asthma. Two groups of subjects with asthma, one group with markedly reactive airways (provocative concentration of methacholine causing a 20% fall in FEV1, 0.07 mg/ml) and the other group with less reactive airways (provocative concentration of methacholine causing a 20% fall in FEV1, 3.83 mg/ml), had allergen bronchoprovocation. After challenge, bronchoconstriction was measured as change in specific airway conductance (SGaw), and mast cell-mediator release was measured as change in both plasma histamine and serum neutrophil chemotactic activity (NCA). In the group with more reactive airways, allergen challenge, while it produced a mean fall in SGaw of 58.1%, was not associated with any significant increase in plasma histamine from a mean resting level of 3.69 nmol/L-1. In contrast, a comparable mean fall in SGaw of 52.4% in the group with less reactive airways was associated with a significant (p less than 0.005) increase in plasma histamine from 1.17 to 3.60 nmol/L-1, maximal 5 minutes after allergen challenge. There were, however, significant increments in serum NCA in both groups with asthma after allergen challenge. The changes in NCA in the group with less reactive airways (136.7 +/- 38.1% above baseline; p less than 0.01; 1% sera dilution) were significantly greater (p less than 0.05) than changes identified in the group with more reactive airways (68.3% above baseline; p less than 0.01; 20% sera dilution). These findings directly support the concept that both mast cell-mediator release and nonspecific bronchial reactivity are separate factors that influence the airway response to inhaled allergen in asthma.(ABSTRACT TRUNCATED AT 250 WORDS)